Microwave assisted synthesis, spectroscopy, crystal structure, characterization and Hirshfeld surface analysis of ureidopeptides and intermediates derived from α,α-dipeptides C-terminal glycine

•Improvement of the primordial peptide cycle activation conditions and sequence.•Description of ureidopeptide/hydantoin crystal packing by H-bonding networks.•FT-IR kinetic analysis and reactivity described for the hydantoin-opening mechanism.•Accurate hydantoin atom localization with HAR from a low quality crystal data.•Hydantoin crystal validation by linear correlation with XRD, DFT and refined by SHELXL. This article describes synthetically useful catabolic pathway activation of the primordial peptide cycle through the effect of microwave irradiation, giving a new variety of peptide derivatives: the α,α-ureidopeptides, as 1,3-disubstituted unsymmetrical ureas via hydantoin, starting from NCbz protected α,α-dipeptide methyl esters containing glycine as the C-terminal residue. The new ureidopeptide series were synthesized and structurally characterized by FT-IR, MS, 1H NMR, 13C NMR spectroscopy, and single-crystal X-ray diffraction analysis. Molecular structure and crystal packing of Phe-Gly-ureidopeptide 3h noted C12H14N2O5, in a monoclinic system and C2/c space group with parameters a = 32.42 Å, b = 9.62 Å, c = 8.40 Å, β=103.25°, and Z = 8, Z’=1, confirm assignations evaluated for the new compounds. The procedure has been extended to the isolation of the α,α-ureidopeptide intermediate, the hydantoin Leu-Gly 4e, C9H14N2O4, demonstrating the synthetic mechanism and crystallized in an orthorhombic system, Pbca space group, with parameters a = 5.19 Å, b = 11.49 Å, c = 35.99 Å, α=β=γ=90°, and Z = 8, Z’=2. Hirshfeld surface analysis on crystal structures of both ureic-derivatives revealed crystal packing relevance and stabilization by the competition of predominant supramolecular interactions easily discernible as nonconventional intermolecular CH•••π, and classical NH•••O or C = OOH•••O = COH, forming complex hydrogen bonding patterns. [Display omitted]